Temple University School of Medicine - Skull Yearbook (Philadelphia, PA)

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New Frontiers at Temple Biochemistry-0. B.-Gyn. One of the several current basic research projects at the Temple University Medical Center is being carried out by the O. B.-Gyn. Department under the direction of Dr. T. Terry Hayashi. That the O.B.-Gyn. Department is involved in basic research illustrates the ramification that a clinical problem can present in an effort to find a solution. Several years ago Dr. T. Terry Hayashi became intrigued by the lack of understanding of the rather common obstetrical entity toxemia of pregnancy. The broad category, toxemia of pregnancy, together with hemorrhage and infection accounted for most of the mortality associated with pregnancy. Dr. Hayashi's preliminary investigations into the physiology of the placenta directed him toward a continually more detailed study of its biochemical activity. From previous studies it seemed apparent that removal of the placenta was the one definitive means of cure, suggesting its possible etiologic role by means of malfunction. A possible clue to malfunction was the phenomenon of hyperuricemia in toxemic women, which cannot be adequately explained on a renal basis. Since uric acid is the end product in man of purine catabolism, it was reasoned that the toxemic placenta may have altered nucleic acid metabolism. The Biochemistry Department provided encouragement, guidance, and initially some facilities for preliminary studies. A program for enzymatic study of the nucleic acid metabolism of the human placenta was set up and the National Institute of Health approved and sponsored the program. In 1959 active work was begun in several small spare rooms on the seventh floor of the Medical School Building. To date, no significant difference between the nucleotide catabolism of normal and toxemic placenta have been uncovered, but in the process much of the purine and pyrimidine metabolic pathways have been elucidated and were reported at the last Federation meeting. Methods for reliable separation of the various purine and pyrimidine compounds in human serum arc now being perfected and the systemic changes in nucleic acid metabolism as reflected in the maternal serum will be studied this coming summer. Radiological Physiology Radiological physiology was begun at Temple by Dr. W. Edward Chamberlain over twenty-five years ago to study physiological mechanisms important in clinical medicine. A large research complex has arisen out of his efforts, the projects of which involve the Departments of Radiology, Physiology, Medical Physics, Medicine, and the Cardiovascular Research Center. This group, now under the leadership of Drs. Herbert M. Stauffer and M. J. Oppenheimer, constitutes one of the foremost team of investigators in the field. Many of the discoveries and developments pioneered by Dr. Chamberlain, former Chairman of the Department of Radiology, Drs. Herbert M. Stauffer, M. J. Openheimer, Bert R. Boone, Thomas M. Durant, George C. Henny, and others have become valuable tools both in medical research and in clinical practice. Stereoscopic biplane angiography and angiocardiography developed at Temple have made possible three-dimensional study of functioning cerebral vessels, tumor circulation, collateral flow around thromboses, and the dynamics of cardiac chambers. Cinefluorography, or the “Xray movie, was another technique developed to study physiological events in vivo. Imagine, intensifiers, which brighten objects as many as three thousand times, combined with high speed exposure cameras have eliminated blurring of fast moving tissues and dark room veiwing. Most importantly the image intensifier has obviated the high doses of patient irradiation once necessary in these studies. Cinefluorography has further been refined by double contrast techniques combining carbon dioxide and diodrast dye in cardiovascular investigation. Cameras have enabled simultaneous recording of phono-cardiograms, electrocardiograms, carotid artery pulsations, and other associated data in the same photograph. Cinefluorography has enabled radiologists all over the world to observe cardiac valvular function, swallowing mechanisms, pericardial effusions, cardiac chambers, and flow patterns in

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of his attitudes and prejudices, the student is better able to treat his patient rationally rather than emotionally. The Comprehensive Medicine Department is also associated with the Center for Community Studies which, under Dr. Herman J. Niebuhr, is attacking many of the social problems of the North Philadelphia area. The Center has recently received a large grant from the Ford Foundation, some of which will go for study of a possible Community Health Center. Artificial Kidney During the summer of 1958, the acquisition of an artificial kidney by the Surgical Research Department extended the special services available at TUH. A special committee was set up headed by Carmen T. Bello, M.D., Associate Professor of Pharmacology and Internal Medicine as chairman, Roger W. Scvy, M.D., Ph.D., Professor and Head of Department of Pharmacology as basic science advisor, Terry T Hayashi, M.D., Associate Professor in Obstetrics and Gynecology, Dominic A. DcLaurenlis, M.D., Associate in Surgery, and William D. Winters, Jr.. M.D., Associate i.n Internal Medicine. This team studied the techniques and principles and solved the technical problems of applying the artificial kidney to the clinical situation. The principles involved in vivodialysis depend on the interposition of a scmipcrmeablc membrane between the patient’s blood and a specially prepared chemical bath. Factors involved determining the direction of flow of ions and molecules across this meinbrancc include concentration gradients, hydrostatic pressures, and the size and configuration of the particles relative to the size of the “pores in the mcmbrancc. Urea, uric acid, creatinine, and other retention products have small molecules and arc freely diffusible.' Water, salts, and glocosc are also freely diffusible allowing for rapid correction of electrolyte abnormalities The membrane is so construced that bacteria, protein, and cellular elements of the blood will not pass through. This differential diffusion is known as dialysis. During dialysis the patient’s heparinized blood is taken from the radial artery to a pumping apparatus that propels the blood under high pressures through twin cellophane coils. These coils are immersed in a tank containing 100 liters of dialyzing fluid. After the blood has crossed the entire length of coil it is returned, dialyzed, to the patient via an available vein. The procedure takes about six hours and as much as 100 grams of urea can be removed from a uremic patient in this time. The surface area of the semipermeable membrane approximates 18,000 square centimeters. The quantity of blood exposed to this membrane during a dialysis is equivalent to fifteen times the patient’s blood volume. The artificial kidney is only an adjunct in the management of renal failure. The best indication for- artificial dialysis is the severe form of acute renal failure which is most likely reversible. It has been and is being used in some medical centers on the patient with chronic renal insufficiency. Presently there is no such program at TUH. Many serious complications can arise from vivodialysis. The artificial kidney is safe and effective only in relation to the knowledge, skill and experience of its operators. 13

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the aorta, vena cavae and other peripheral vessels. Electrokymography, designed at Temple in 1945 by Drs. Chamberlain, Boone, and Henry, has been used extensively in Europe in studying cardiac border movements and silhouette densities. It is based on recording changes in movement and density of the heart onto a fluoroscopic screen and converting the picture into electrical patterns. These are only a few of the projects on which Dr. Stauffer's group has been engaged. They serve to reemphasize the leading role Temple has played in the field-of radiologic research and its clinical application. Stereotaxic Surgery For the past fifteen years, Drs. Wycis and Spiegel have been working with new surgical methods in an effort to devise surgical treatment for diseases of the brain. Perhaps the best known contribution of this distinguished Temple team has been the application of stereotaxic surgery to such disorders as Parkinsonism. In the late nineteen thirties and early nineteen forties surgeons around the world, in particular a Dr. Mayers at Iowa, stumbled onto the area of the brain responsible for the shaking and tremor seen in Parkinsonism and other such disorders — the area of basal ganglia Now it remained for surgeons to find a way to hit that target area in the brain without unduly harming other areas. The first step was taken by the team at Temple University Medical Center, headed by world famous neurophysiologist, Dr. Ernest Spiegel, and one of his brilliant American students, Dr. Henry Wycis. Together they developed a special machine for aiming electrodes into localized areas of the brain. This device is called a stcreoencephalotome. Then the two men devised a new kind of brain map enabling doctors, by mathematical calculations, to find the exact location of any brain center. Through the use of the stereoencephaloiome and the brain atlas Drs. Spiegel and Wycis have been able to pass electrodes into the basal ganglia and destroy parts of such brain centers. Today the two men continue to work exploring new centers in the brain, looking for new and better methods of application of the stcreoencephalotome. Such disorders as cerebral palsy and epilepsy also may be helped by the continued work of these two great pioneers. Pels Institute The Samuel S. Fcls Research Institute has its inception in 1933 and Dr. Harry Shay has been its Director since then. The major areas of research being investigated are gastroenterology, both basic physiology and clinical research, and cancer research. The complete personnel of the Institute now numbers sixty-two, including seven physicians, four Ph.Ds, three with Masters, along with many technicians at the Bachelor adadcmic level. The facilities are curently housed in the Medical School and at Barton Hall Until the new research building is available for occupancy, the latter houses the laboratories of Dr. Sidney Weinhouse. who joined the Institute in January 1962, as Associate Director of the Institute as well as Professor of Biochemistry in the Medical School. ’lTte Institute will also occupy the seventh and eighth floors in the new- research building, thus, greatly enlarging its present facilities. This will permit an increase of our research staff. Several additional senior investigators are contemplated and one very important investigator, Dr. Michael Shimkin, will be joining both the Medical School and the Institute in July. Dr. Shimkin is now Associate Director for field studies of the National Cancer Institute and Scientific Editor of the Journal of the National Cancer Institute. He is also Chairman of the Ad Hoc Research Advisory Committee on Breast Cancer for the American Cancer Society. Dr. Shimkin will be Professor of Medicine in the Medical School and Chief of Cancer Biology in the Institute. The expanding Institute currently has budget of over $500,000. In gastroenterology the research areas have included basic physiology, gastric secretion and motility, pancreatic function with the development of an adequate pancreatic function profile. In the liver area, jaundice and sensitization of the liver to drugs have been the major areas of investigation. The Fcls Research Institute has been in a large measure responsible for the development of the rat as an experimental tool in gastric secretion. One such preparation, in use very extensively for many years and referred to in the literature as the Shay rat, has been the experimental tool used by investigators in over five hundred publications. Dr. Komarov and Dr. Bralow have recently developed a chronic gastric fistula in the rat which promises to enhance even more the value of this animal in research in gastrointestinal physiology. We expect to utilize this preparation in the detailed study of the effect of the endocrine glands on gastric secretion over the next two or three years. In the cancer area the Institute has developed two major methods of investigation. One, is a method for the induction of myelogenous leukemia in the rat which is readily transferred. This preparation has been shipped to more than forty research laboratories around the world where the preparation is in use for research in leukemia. Another important tool that has been developed in the laboratory is a method for the development of breast cancer in female rats in very high incidence and the study of this tumor to show that in its hormonal relationships it very closely mimics the behavior of human breast cancer. In the past two years this system has been modified to produce reproducible breast cancer in low incidence, a system that will lend itself admirably for the study of cocarcinogcnic and promoting agents. Particularly applicable will this system be for a search for these agents in foods and food additives. Furthermore, our method for the induction of breast cancer in the rat has also made possible the development of a system for the study of cancer chemotherapeutic agents. It is for the development of this system that the Institute was awarded a contract by the Cancer Chemotherapy National Service Center some two years ago. The biochemical studies are concerned largely with the chemistry of the cancer cell and with glucose metabolism 15